Abstract
Background: Stroke is the leading cause of serious long-term disability. Currently, there is no effective treatment for chronic stroke patients. Neuroplasticity within motor circuitry is believed to support recovery of function after stroke. We have developed a method using vagus nerve stimulation (VNS) paired with motor training to drive robust, specific plasticity in the motor cortex. Our recent studies indicated that VNS paired with rehab training significantly enhances recovery of forelimb function after cortical ischemic stroke. To further the translation potential of our therapy, we accessed the hypothesis that delivering VNS paired with rehab may improve functional recovery in rats that demonstrated chronic forelimb impairments. Methods: All female Sprague Dawley rats were trained on the Isometric Pull Task, which quantifiably measures forelimb force generation. Rats that achieved 5 consecutive days of over 85% hit rate on this task were given a unilateral cortical-subcortical ischemic lesion via injections of a vasoconstrictive peptide, endothelin-1. Following the lesion, rats returned to their home cage, and did not begin rehab training until 5 weeks post-lesion. Upon return, post-lesion forelimb impairment was accessed with the same task parameters used during pre-lesion training, which allowed for a direct comparison of performance. Rats were assigned to balanced treatment groups based on post-lesion baseline hit rate. Treatment groups consisted of VNS delivered during rehab training (Paired VNS; n=10), VNS delivered two hours after rehab training (Delayed VNS; n=10), and rehab training without VNS (Rehab; n=10). Results: At five weeks post-lesion, the unilateral ischemic insult significantly worsened performance in all three groups compared to pre-lesion (Paired VNS: 29.8 ± 5.7%, paired t-test, P < 0.001; Delayed VNS: 24.6 ± 2.7%, P < 0.001; Rehab: 30.4 ± 4.7%, P < 0.001). Following our therapy, the Paired VNS group demonstrated significantly better performance than both control groups (Paired VNS: 81.6 ± 2.3%, P < 0.01; Delayed VNS: 53.2 ± 6.5%, P < 0.01; Rehab: 49.8 ± 6.8%, P < 0.01). Conclusion: Our results indicate that VNS paired with rehab training can further enhance recovery of forelimb function in chronically impaired rats.
Published Version
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